, Volume 20, Issue 2, pp 209-219

Suramin's Development: What Did we Learn?

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Abstract

Suramin, a polysulphonated napthylurea, has been extensively evaluatedover the past 10 years as an anticancer agent, with the most interest inthe treatment of prostate cancer. Early clinical results were promisingwith response rates of up to 70% being reported. However, a recentdouble-blind study showed only modest palliative effect in patients withandrogen independent prostate cancer. In retrospect, it appears thoseinitial reports failed to control for confounding variables such asantiandrogen withdrawal and hydrocortisone.

Suramin causes numerous reversible toxicities (lethargy, rash, fatigue,anemia, hyperglycemia, hypocalcemia, coagulopathies, neutropenia, renaland hepatic complications). Neurotoxicity has been the most significantcomplication and appears to be related to the intensity of the dosingregimen. An optimal therapeutic dose has not been determined, but it isclear that adaptive controls add little benefit.

Aside from moderate toxicities and the low therapeutic index in patientswith prostate cancer, suramin's development has taught us some valuablelessons (i.e., anti-androgen withdrawal was noted during suramin'sdevelopment, the use of PSA as an indicator of tumor burden was initiatedduring the evaluation of suramin). These lessons can be applied to allclinical trials in hormone refractory prostate cancer. Suramin hassignificantly enhanced the evolution of our knowledge in several areas ofprostate cancer biology and treatment.